Development of a Numerical Model for Microbubble-Enhanced Treatment in HIFU Therapy High Intensity Focused Ultrasound (HIFU) is currently utilized in several modern therapeutic and surgical medical applications, such as for tissue ablation in the treatment of cancer and for benign prostatic hyperplasia. The HIFU research frontier has now moved toward the treatment of deep-seated solid tumors such as in liver and brain cancers because HIFU is a truly noninvasive form of localized ablative therapy. To eliminate pre-focal damage due to induced cavitation activity along the pathway, microbubbles used as ultrasonic contrast agents have been proposed to be injected into the targeted region to promote heating through controlled bubble dynamics activity in the focal region, while reducing the HIFU source intensity. The behavior of such injected microbubbles and their interaction with the acoustic field has not been fully investigated experimentally or numerically due to the complex nonlinear interactions between the oscillating bubbles and the ultrasound. In this SBIR Phase II effort, continuation of the development of a novel numerical approach is proposed to help accurately characterize the acoustic and thermal field in microbubble-enhanced HIFU under various conditions. The numerical approach employs an Eulerian- Lagrangian approach in which the bubbles are tracked in a Lagrangian fashion, while the acoustic and thermal fields are resolved using a fixed grid Eulerian continuum approach. The heat deposition in the HIFU focal region, contributed by both the ultrasound acoustic waves and the bubble oscillations, will be modeled by solving heat transport equations. The two-way coupling allows to predict the nonlinear acoustic field and bubble behaviors accurately and accounts for both bubble-bubble and bubble-fluid interaction. A multi-level parallelization algorithm using both Graphic Processing Unit (GPU) and Central Processing Unit (CPU) computation technology will be implemented to speed up the computations. The developed numerical model has been successfully validated against experimental data available in the literature during Phase I. In Phase II in vitro and ex vivo experiments using machine-perfused pig liver will be conducted at the University of Washington for further in-depth validation. These will form an important stepping stone for future large animal studies followed by clinical trials. The resulting product will be a computational tool useful to help researchers develop efficient microbubble-enhanced HIFU for the treatment of deep-seated solid tumors. The tool will be also utilized by HIFU instrument manufacturers to select, using parametric studies, efficient and safe designs and by medical researchers to design proper HIFU treatment protocol for clinicians. The software will also be applicable to the modeling of other controlled cavitation bubbles such as those generated by shock wave lithotripter.